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Spatial heterogeneity of the relation between resting-state connectivity and blood flow: an important consideration for pharmacological studies.

ABSTRACT: Resting state fMRI (RSfMRI) and arterial spin labeling (ASL) provide the field of pharmacological Neuroimaging tool for investigating states of brain activity in terms of functional connectivity or cerebral blood flow (CBF). Functional connectivity reflects the degree of synchrony or correlation of spontaneous fluctuations--mostly in the blood oxygen level dependent (BOLD) signal--across brain networks; but CBF reflects mean delivery of arterial blood to the brain tissue over time. The BOLD and CBF signals are linked to common neurovascular and hemodynamic mechanisms that necessitate increased oxygen transportation to the site of neuronal activation; however, the scale and the sources of variation in static CBF and spatiotemporal BOLD correlations are likely different. We tested this hypothesis by examining the relation between CBF and resting-state-network consistency (RSNC)--representing average intranetwork connectivity, determined from dual regression analysis with eight standard networks of interest (NOIs)--in a crossover placebo-controlled study of morphine and alcohol. Overall, we observed spatially heterogeneous relations between RSNC and CBF, and between the experimental factors (drug-by-time, time, drug and physiological rates) and each of these metrics. The drug-by-time effects on CBF were significant in all networks, but significant RSNC changes were limited to the sensorimotor, the executive/salience and the working memory networks. The post-hoc voxel-wise statistics revealed similar dissociations, perhaps suggesting differential sensitivity of RSNC and CBF to neuronal and vascular endpoints of drug actions. The spatial heterogeneity of RSNC/CBF relations encourages further investigation into the role of neuroreceptor distribution and cerebrovascular anatomy in predicting spontaneous fluctuations under drugs.

SUBMITTER: Khalili-Mahani N

PROVIDER: S-EPMC6869220 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Spatial heterogeneity of the relation between resting-state connectivity and blood flow: an important consideration for pharmacological studies.

Khalili-Mahani Najmeh N van Osch Matthias J MJ de Rooij Mark M Beckmann Christian F CF van Buchem Mark A MA Dahan Albert A van Gerven Johannes M JM Rombouts Serge A R B SA

Human brain mapping 20121226 3

Resting state fMRI (RSfMRI) and arterial spin labeling (ASL) provide the field of pharmacological Neuroimaging tool for investigating states of brain activity in terms of functional connectivity or cerebral blood flow (CBF). Functional connectivity reflects the degree of synchrony or correlation of spontaneous fluctuations--mostly in the blood oxygen level dependent (BOLD) signal--across brain networks; but CBF reflects mean delivery of arterial blood to the brain tissue over time. The BOLD and ...[more]

PMID: 23281174

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Project description:The human brain at rest exhibits intrinsic dynamics transitioning among the multiple metastable states of the inter-regional functional connectivity. Accordingly, the demand for exploring the state-specific functional connectivity increases for a deeper understanding of mental diseases. Functional connectivity, however, lacks information about the directed causal influences among the brain regions, called effective connectivity. This study presents the dynamic causal modeling (DCM) framework to explore the state-dependent effective connectivity using spectral DCM for the resting-state functional MRI (rsfMRI). We established the sequence of brain states using the hidden Markov model with the multivariate autoregressive coefficients of rsfMRI, summarizing the functional connectivity. We decomposed the state-dependent effective connectivity using a parametric empirical Bayes scheme that models the effective connectivity of consecutive windows with the time course of the discrete states as regressors. We showed the plausibility of the state-dependent effective connectivity analysis in a simulation setting. To test the clinical applicability, we applied the proposed method to characterize the state- and subtype-dependent effective connectivity of the default mode network in children with combined-type attention deficit hyperactivity disorder (ADHD-C) compared with age-matched, typically developed children (TDC). All 88 children were subtyped according to the occupation times (i.e., dwell times) of the three dominant functional connectivity states, independently of clinical diagnosis. The state-dependent effective connectivity differences between ADHD-C and TDC according to the subtypes and those between the subtypes of ADHD-C were expressed mainly in self-inhibition, magnifying the importance of excitation inhibition balance in the subtyping. These findings provide a clear motivation for decomposing the state-dependent dynamic effective connectivity and state-dependent analysis of the directed coupling in exploring mental diseases.

Dataset Information

Spatial heterogeneity of the relation between resting-state connectivity and blood flow: an important consideration for pharmacological studies.

Publications

Spatial heterogeneity of the relation between resting-state connectivity and blood flow: an important consideration for pharmacological studies.

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